Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive imaging technique to assess brain function. The technique is non-invasive and portable and therefore applicable in studies of children and toddlers especially those with neurodevelopmental disorders. fNIRS measurements are based on the local changes in cerebral hemodynamic levels (oxy-hemoglobin and deoxy-hemoglobin) associated with brain activity. Due to the low optical absorption of biological tissues at NIR wavelengths (700-900 nm), NIR light can penetrate deep enough to probe the cortical regions up to 1-3 cm deep. The NIR absorption spectrum of the tissue is sensitive to changes in the concentration of major tissue chromophores, such as hemoglobin. Therefore, measurements of temporal variations of backscattered light can capture functionally evoked changes in cortex to assess the brain function. Two general tracks of research involving fNIRS in the brain are currently being pursued in our lab: developmental trajectories of cognitive abilities, and the comparison of fNIRS to cognitive tasks that have been evaluated using fMRI. Previous studies that we have conducted examined measures of prefrontal cortical activation using fNIRS as they relate to developmental level in toddlers. We have continued this work in 2019 through a series of projects and collaborations. First, as part of a previous collaboration with Dr. Audrey Thurm (NIMH), we have begun another project which will examine the developmental trajectory of the mirror neuron network in infants (IRB # 18-CH-0001). The mirror neuron network (MNN) is associated with the development of sophisticated social behaviors that emerge in typical human infants (e.g., complex imitation, decoding emotional states). Modeling MNN development will create a sensitive measure of deviations in social communication development before clinical behavioral deficits can be detected. MNN activation has already been associated with Mu suppression using EEG. Using EEG (with high temporal resolution) in conjunction with fNIRS will provide more precise spatial resolution of neural activity based on hemodynamic activation to investigate the MNN. In the pilot study, we have recruited healthy adults (N=40) to see whether MNN activation can be elicited using a motor observation and execution paradigm and recorded through an EEG/fNIRS system simultaneously. Throughout the piloting process we adjusted the paradigm to optimize it for combined EEG/fNIRS data collection. We have collected data from 21 participants using the finalized paradigm and are in the process of examining the synchronicity of these signals as they relate to social communication and cognitive functioning. We are continuing collection in adult pilot subjects until we achieve a sample size of 40 participants using the finalized paradigm, and plan to have a manuscript of these findings submitted by October 2019. We are simultaneously preparing for the recruitment of typically developing infants (9-12 months) (n=60) and infants at-risk for developmental delays (n=60) to complete this paradigm. At-risk infants will be brought in again at 24 months of age to evaluate any deviations in their social communicative development. Their developmental status will be examined in relation to their initial neural data to see if MNN activation at this age can predict developmental outcomes. We aim to begin recruiting infants for this phase of the project in October 2019. Through a collaboration with Dr. Andrea Gropman at Childrens National Medical Center, we are examining developmental deficits in children with Urea Cycle Disorders (UCD). UCDs are a set of rare genetic disorders caused by the loss of enzymatic activities (such as transcarbamylase deficiency (OTCD)) that mediate the transfer of nitrogen from ammonia to urea. UCD often results in life-threatening hyperammonemia resulting in a broad range of neurological impairments in working memory and executive function. Dr. Gropman, world renowned expert on UCD, found that patients with OTCD showed impairments in frontal lobe processing through their performance on a working memory task compared to a control group using fMRI. We are replicating this work using fNIRS. We have recorded hemodynamic activity from prefrontal cortex from 26 children and adults (control and with UCD) while performing n-back and color and word Stroop tasks. Data collection for this project for 40 subjects is near completion, and data processing is underway. Lastly, as part of our ongoing fNIRS calibration protocol (IRB #10-CH-0198), a paper was published examining working memory in typically developing adults revealing that activation in the prefrontal cortex changes over the course of a working memory task. Furthermore, in this same set of subjects, performance on the working memory task improved, indicating that there may be a practice effect taking place. Other studies under this protocol were also developed over the past year. One study implemented simultaneous fNIRS and heart rate variability measurement to examine the relationship between these variables at rest and during a behavior inhibition task. We hypothesized that prefrontal activation would be correlated with heart rate variability, a measure of parasympathetic nervous system activation, based on tenants of the neurovisceral integration model. Our hypothesis was confirmed through our analyses and the manuscript is currently under review for publication. Additionally, we are currently conducting analyses for another manuscript based on these data to study to examine neural activation patterns during an inhibition task, the go/no-go task. The go/no-go task is an executive function task which activates prefrontal cortical areas, as previously established through fMRI research. In the present study, the go/no-go task was administered to 44 typically developing adults while fNIRS and was recorded. The goal of this study was to establish the utility of fNIRS in evaluating prefrontal activation during a behavior inhibition task. We found that fNIRS distinguished differences between baseline and the go/no-go task, and could be a suitable alternative to fMRI in the evaluation of behavior inhibition. Data are being further analyzed to see if fNIRS measurements are related to individuals level of task performance, or to more general measures of day-to-day behavior inhibition abilities (e.g., self-report). Analysis is ongoing, with the goal of submitting a manuscript by September 2019. Another project under the Calibration protocol is currently under development to further examine prefrontal activation in healthy adults using fNIRS during other executive functioning tasks. Specifically, we are incorporating additional executive function tasks involving inhibition beyond the go/no-go (e.g., the Flanker task, the Stroop task) to see whether brain activation varies as a function of 1. the type of inhibition task, and 2. successful inhibition attempts versus unsuccessful inhibition attempts in healthy adult subjects. Detecting differences between these types of tasks will allow us to find more specific neural signatures of the subcomponents involved in the complex process of behavior inhibition. These components are shown to lead to slightly different behavioral manifestations that are associated with behavior inhibition deficits seen across developmental disorders, such as ADHD and autism spectrum disorder. The developing study will allow us to establish the most appropriate tasks to use in evaluating various aspects of behavior inhibition affected in these disorders and to determine whether fNIRS can adequately measure the brains response to these tasks, so that these methods may then be applied in future work we plan to conduct in these populations.